DESCRIPTION My ultimate goal is to develop therapies based on an understanding of the mechanisms of human movement and how that understanding can be utilized to re-train walking in the most effective manner possible. A fundamental understanding of the specific mechanisms underlying locomotor dysfunction is required for developing individualized rehabilitation programs targeting improved walking performance. Therapists will improve clinical decision-making if detailed knowledge of the relationship between these mechanistic underpinnings and response to rehabilitation allows them to target specific neuromechanical contributors to motor dysfunction. Furthermore, knowledge of how individuals with neurological impairments adapt to training tasks will assist in the optimization of treatment programs, which essentially aim to promote long-term learning. This application reflects the goal of indivually-based, theory-driven interventions by targeting specific biomechanical elements of walking, assaying motor learning, and applying adjunctive non-invasive electrical stimulation to decrease neural activation impairments. The proposed work will continue my training in motor control and learning under my current CDA-1 mentor Dr. Steven Kautz. An exciting new element that will be incorporated into the proposed work is electrical stimulation of the brain as an intervention to potentially improve motor adaptations and motor learning potential. I will attain this new skill under the direction of mentor Dr. Mark George, a world leader in brain stimulation and a physician investigator at the Ralph H. Johnson VA Medical Center. The proposed project seeks to identify effective strategies for training a specific locomotor adaptation, to establish the optimal configuration of electrodes to activate neural circuits involved in post-stroke locomotion, and to improve adaptations via adjunctive non- invasive brain stimulation. Over the next five years, we propose to focus on three specific goals: 1) develop skills associated with applying transcranial direct current stimulation (tDCS) for locomotor recovery post-stroke; 2) progress motor adaptation assessment skills; and 3) perform a foundational research study that prepares investigator for subsequent Merit Award. For Goal 1, we will recruit 40 individuals with chronic stroke (greater than six months post-stroke) in order to determine the optimal configuration of tDCS to elicit immediate lower extremity muscle activation in those with post-stroke hemiparesis. Recent investigations of tDCS in the upper extremity post-stroke indicate that ipsilesional excitation and contralesional inhibition are both effective at increasing motor control, but we hypothesize that a combination of the two placements will produce the largest improvements in lower extremity motor activation and interlimb coordination required for a locomotor task. For Goal 2, we will recruit 40 individuals with chronic stroke to distinguish between two approaches (treadmill incline walking and COM-assisted walking) for retraining the center of mass acceleration (COMa) in those post-stroke presenting with propulsion deficits. For this goal, we hypothesize that treadmill incline walking will demonstrate normalization of the COMa curve, increased paretic propulsion, and improved smoothness of the COMa curve (harmonic ratio) > COM-assisted walking > than walking on a treadmill alone. Lastly, for Goal 3 we will enroll the same 40 individuals from Goal 2 to determine the effect of combining tDCS with COMa training. We hypothesize that training with the optimal electrode configuration (determined in Aim 1) and the optimal method for training COMa (determined from individual assessments in Aim 2) will be superior to training COMa with sham stimulation. Furthermore, we hypothesize that multiple days of training will increase cortical excitability and demonstrate improved modification of the COMa. This work will not only yield important contributions to the literature regarding motor learning specific to locomotion, but also will provide the necessary information to propose a Merit Award at the end of the Career Development period. PUBLIC HEALTH RELEVANCE: This project will evaluate two different methods of normalizing the center of mass acceleration (COMa) in individuals post-stroke, specifically focusing on rates and pattern of recovery to analyze walking-specific adaptations as precursors to motor learning. In addition, the proposed project seeks to establish the optimal configuration of electrodes to activate neural circuits involved in post-stroke locomotion. Once the better method of training COMa and optimal parameters of electrode placement for tDCS are identified, we will evaluate the effects of tDCS on locomotor adaptations during single sessions and over a five-day training period.